Embodiments of the invention are directed to an apparatus and method for fully automated, noninvasive system to prepare hyperpolarizing imaging agents for use in magnetic resonance imaging (MRI). More specifically, embodiments of the invention relates to an apparatus and method for noninvasively polarizing, filtering, and performing quality control testing of the hyperpolarizing imaging agents prior to introduction to a subject being imaged.
MRI is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially any harmful exposure such as from X-rays. Analytical high resolution NMR spectroscopy is routinely used in the determination of molecular structure.
MRI and NMR spectroscopy lack some degree of sensitivity due to the normally very low polarization of the nuclear spins of the contrast agents typically used. A number of techniques exist to improve the polarization of nuclear spins. These techniques are known as hyperpolarization techniques and lead to an increase in sensitivity. In hyperpolarization techniques, a sample of an imaging agent, for example 13C-Pyruvate or another agent, is introduced or injected into the subject being imaged.
In many instances, the imaging agent undergoes this hyperpolarization in an apparatus in close proximity to its end use. This is due to the normally short lifetime (longitudinal relaxation time T1) of the polarization causing the spins to relax back to the thermal equilibrium polarization. One technique to address the normally short lifetime is to use Dynamic Nuclear Polarization to polarize the spins in the solid state. Apparatuses used to produce the hyperpolarized samples are provided with a low temperature space that is in a magnetic field. As typically constructed, the apparatus is equipped with a flow cryostat that includes a vacuum insulated chamber inserted into the bore of a magnet. The cryostat is cooled by way of a stream of a cold cryogen provided by an external cryogen supply through a transfer line and pumping device, and the flow of cryogen into the flow cryostat cools the bore of the magnet and forms the low temperature space.
The imaging agent is transferred to the cryostat where hyperpolarization occurs through interaction with an Electron Paramagnetic Agent (EPA) within a magnetic field. The now cryogenically frozen material is subsequently dissolved in a dissolution material delivered by way of a fluid path delivery system. A second fluid path system is used to displace the dissolved material from the polarizer.
Once removed from the polarizer, the now dissolved hyperpolarized imaging agent is filtered to remove the EPA and other additives. A receiver vessel is used to collect the pharmacological product and allow for quality control (QC) testing of the material prior to being released for a patient.
The hyperpolarized imaging agent produced in this manner is sensitive to handling and environmental conditions, exacerbated by its short lifetime. These can affect the safety and efficacy of the imaging agent. Other difficulties in production are associated with the need to QC test multiple variables within a short time period while sterility and efficacy is maintained.
Furthermore, current hyperpolarization systems are inefficient and expensive to operate. For example hyperpolarization requires high cryogen consumption and is energy and labor intensive, often requiring the operator to handle liquid cryogens and guide and insert samples into the polarizer. It is thus desirable that an improved hyperpolarization system be designed to operate in a manner that minimizes disruption to the surrounding environment, allow more continuous operation, without the requirement of the operator to handle liquid cryogens, and to increase throughput of the hyperpolarized imaging agent samples.
Therefore what is needed is a fully automated, noninvasive apparatus and method adapted to the preparation of one or more hyperpolarized imaging agent for delivery to its end-use while preserving the sterility, safety and efficacy of the imaging agent.